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Epithelial Ca²⁺ and Mg²⁺ Channels in Health and Disease

Department of Physiology, Nijmegen Center for Molecular Life Sciences, Radboud University Nijmegen Medical Center, the Netherlands

Address correspondence to: Dr. René J.M. Bindels, 160 Cell Physiology, Radboud University Nijmegen Medical Center, P.O. Box 9101, 6500 HB Nijmegen, the Netherlands. Phone: +31-24-3614211; Fax: +31-24-3616413; r.bindels{at}ncmls.ru.nl

A near constancy of the extracellular Ca²⁺ and Mg²⁺ concentration is required for numerous physiologic functions at the organ, tissue, and cellular levels. This suggests that minor changes in the extracellular concentration of these divalents must be detected to allow the appropriate correction by the homeostatic systems. The maintenance of the Ca²⁺ and Mg²⁺ balance is controlled by the concerted action of intestinal absorption, renal excretion, and exchange with bone. After years of research, rapid progress was made recently in identification and characterization of the Ca²⁺ and Mg²⁺ transport proteins that contribute to the delicate balance of divalent cations. Expression-cloning approaches in combination with knockout mice models and genetic studies in families with a disturbed Mg²⁺ balance revealed novel Ca²⁺ and Mg²⁺ gatekeeper proteins that belong to the super family of the transient receptor potential (TRP) channels. These epithelial Ca²⁺ (TRPV5 and TRPV6) and Mg²⁺ channels (TRPM6 and TRPM7) form prime targets for hormonal control of the active Ca²⁺ and Mg²⁺ flux from the urine space or intestinal lumen to the blood compartment. This review describes the characteristics of epithelial Ca²⁺ and Mg²⁺ transport in general and highlights in particular the distinctive features and the physiologic relevance of these new epithelial Ca²⁺ and Mg²⁺ channels in (patho)physiologic situations.

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